While excessive alcohol intake can result in alcoholic cardiomyopathy, hypertension and arrhythmias, some epidemeologic studies suggest that moderate alcohol intake could actually be good for the heart and may reduce the incidence of coronary artery disease. Suggested mechanisms for the beneficial effects include an elevation of high density lipoprotein, prevention of platelet aggregation, increased fibrinolysis, and now a possible direct effect of moderate alcohol on the heart that includes similar pathways to the protective effects observed with ischemic preconditioning. This proposal will: 1) test the hypothesis that chronic moderate pulsatile consumption of alcohol (resulting in peak blood levels of 5-10 mM) will reduce myocardial infarct size, arrhythmias, and the no-reflow phenomenon in rats subjected to coronary artery occlusion followed by reperfusion, and 2) test the hypothesis that the mechanistic pathways involved in this protection are similar to those described in ischemic preconditioning, including protein kinase C and KATP-channel activation, as well as up-regulation of heat shock proteins. We propose a 6-month pilot phase to adjust alcohol doses as needed to achieve the desired alcohol level. The techniques of coronary artery ligation in the rat, measurement of infarct size using triphenyltetrazolium chloride and risk zone using blue dye, and quantification of regional myocardial blood flow using radiolabeled microspheres and hemodynamic measurements are standard in this laboratory. The significance of these findings include establishing mechanisms by which alcohol could have a beneficial effect on ischemic myocardium leading to potential new therapies for ischemia/reperfusion.